PARP1 (PDB: 4DQY) — catalytic core resolves NAD⁺ positioning (H133/E134/Mg²⁺) and substrate interface (326–332) as structurally separable sites. E134 as the ADP-ribose acceptor base.
Age-associated DNA damage → PARP1 hyperactivation → NAD⁺ depletion → SIRT1/3 inactivation → mitochondrial dysfunction. A structurally grounded feedforward loop in biological aging.
#PARP1 #NAD #StructuralBiology #LongevityBiology #Aging #DNARepair #Biogerontology #Sirtuins

